Protein N-terminal acetylation is a major
modification of eukaryotic proteins. Its functional implications
include regulation of protein–protein interactions and
targeting to membranes, as demonstrated by studies of a
handful of proteins. Fifty years after its discovery, a potential
general function of the N-terminal acetyl group carried by
thousands of unique proteins remains enigmatic. However,
recent functional data suggest roles for N-terminal acetylation
as a degradation signal and as a determining factor
for preventing protein targeting to the secretory pathway,
thus highlighting N-terminal acetylation as a major
determinant for the life and death of proteins. These
contributions represent new and intriguing hypotheses that
will guide the research in the years to come.